Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

OBJECTIVES: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury. DESIGN: Prospective, longitudinal imaging study. SETTING: Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA). SUBJECTS: Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome). INTERVENTIONS: Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics. MEASUREMENTS AND MAIN RESULTS: Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects. CONCLUSIONS: The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.

Evaluation of Miniature Dynamic Light Scattering Technology for the Assessment of Hemodynamic Status During Graded Hemorrhage and Retransfusion in Pigs.

BACKGROUND: Hemorrhagic shock with occult hypoperfusion is a key challenge to prehospital staff during triage and transfer of patients, especially during mass casualty incidents. Recent advances in Dynamic Light Scattering (DLS), and miniaturization of this technology, has resulted in noninvasive sensors capable of continuously monitoring tissue perfusion. This study evaluated the ability of miniature DLS (mDLS) sensors to assess hemodynamic status in a porcine model of hemorrhage. METHODS: Following ethics committee approval, anesthetized and ventilated pigs underwent graded hemorrhage and then retransfusion. Standard vital signs were monitored in conjunction with a thermodilution cardiac output (CO), central venous pressure (CVP), and arterial blood gases. The mDLS sensor was attached to each animal's leg and all monitoring measurements were taken 5 minutes after completion of each period of hemorrhage and retransfusion to allow equilibration. RESULTS: All measured parameters changed during bleeding and retransfusion. During bleeding; p value were 0.011 for heart rate, 0.07 for CVP, <0.001 for both mean arterial pressure, and mDLS. During retransfusion; p values were 0.023 for heart rate, 0.008 for CVP, and <0.001 for both mean arterial pressure and mDLS. Pearson correlation between changes in mDLS and CO demonstrated r value of 0.917 during hemorrhage and 0.965 during retransfusion. Changes in hemoglobin were not statistically significant during bleeding (p = 0.331) but were during retransfusion (p = 0.0001). Changes of bicarbonate, base excess, and lactate were found to be statistically significant during both phases of the experiment (p = 0.001). CONCLUSIONS: In an animal model of hemorrhagic shock, the mDLS sensor strongly correlates with traditional measures of CO. This initial assessment supports further investigation of this technology in human studies.

Thromboelastography during coronary artery bypass grafting surgery of severe hemophilia A patient - the effect of heparin and protamine on factor VIII activity.

: Coronary artery bypass grafting surgery (CABG) in hemophilia patients is challenging. Thromboelastography (TEG) is useful to assess hemostasis perioperatively. A patient with severe hemophilia A underwent CABG with TEG studies. After factor VIII (FVIII) bolus dose, TEG was normalized. Following 'on-pump' heparinization, protamine administration revealed prolonged TEG-R and TEG-R with heparinase confirming it, whereas the activated clotting time was normal, suggesting low FVIII activity rather than excess of heparin. Another FVIII bolus yielded complete normalization of all TEG parameters. Data are compatible with in-vitro assays performed in our laboratory, showing that both heparin and protamine may impair measurable FVIII activity. The rational use of TEG measurements enabled more accurate hemostatic therapy application with regard to FVIII, heparin and protamine administration. Adopting this approach may lead to a better therapy tailoring for hemophilia patients undergoing CABG surgery.

Severity of acute kidney injury and two-year outcomes in critically ill patients.

BACKGROUND: The association between levels of acute kidney injury (AKI) during ICU admission and long-term mortality are not well defined. METHODS: We examined medical records of adult patients admitted to a large tertiary medical center with no history of end-stage renal disease who survived 60 days from ICU admission between 2001 and 2007. Demographic, clinical, physiologic, and date of death data were extracted. RESULTS: Among 15,048 patients, 12,399 (82.4%) survived 60 days from ICU admission and comprised the study population. AKI did not develop in 5,663 (45.7%) during ICU admission, whereas progressively severe levels of AKI as defined by Acute Kidney Injury Network (AKIN) criteria AKIN 1, AKIN 2, and AKIN 3 developed in 4,589 (37.0%), 1,613 (13.0%), and 534 (4.3%), respectively. Only 42.5% of patients with AKIN 3 survived 2 years from ICU admission. Patients with AKIN 3 had a 61% higher mortality risk 2 years from ICU discharge compared with patients in whom AKI did not develop. Patients with AKIN 1 and AKIN 2 had similar increased mortality risk 2 years from ICU admission (hazard ratio, 1.26 and 1.28, respectively). The level of estimated glomerular filtration rate on ICU discharge and chronic kidney disease were associated with long-term mortality. CONCLUSIONS: Patients in whom AKI develops during ICU admission have significantly increased risks of death that extend beyond their high ICU mortality rates. These increased risks of death continue for at least 2 years after the index ICU admission.

Empirical relationships among oliguria, creatinine, mortality, and renal replacement therapy in the critically ill.

PURPOSE: The observation periods and thresholds of serum creatinine and urine output defined in the Acute Kidney Injury Network (AKIN) criteria were not empirically derived. By continuously varying creatinine/urine output thresholds as well as the observation period, we sought to investigate the empirical relationships among creatinine, oliguria, in-hospital mortality, and receipt of renal replacement therapy (RRT). METHODS: Using a high-resolution database (Multiparameter Intelligent Monitoring in Intensive Care II), we extracted data from 17,227 critically ill patients with an in-hospital mortality rate of 10.9 %. The 14,526 patients had urine output measurements. Various combinations of creatinine/urine output thresholds and observation periods were investigated by building multivariate logistic regression models for in-hospital mortality and RRT predictions. For creatinine, both absolute and percentage increases were analyzed. To visualize the dependence of adjusted mortality and RRT rate on creatinine, the urine output, and the observation period, we generated contour plots. RESULTS: Mortality risk was high when absolute creatinine increase was high regardless of the observation period, when percentage creatinine increase was high and the observation period was long, and when oliguria was sustained for a long period of time. Similar contour patterns emerged for RRT. The variability in predictive accuracy was small across different combinations of thresholds and observation periods. CONCLUSIONS: The contour plots presented in this article complement the AKIN definition. A multi-center study should confirm the universal validity of the results presented in this article.

Outcome of critically ill patients with acute kidney injury using the Acute Kidney Injury Network criteria.

OBJECTIVE: Acute kidney injury affects 5% to 7% of all hospitalized patients with a much higher incidence in the critically ill. The Acute Kidney Injury Network proposed a definition in which serum creatinine rises (>0.3 mg/dL) and/or oliguria (<0.5 mL/kg/hr) for a period of 6 hrs are used to detect acute kidney injury. Accurate urine output measurements as well as serum creatinine values from our database were used to detect patients with acute kidney injury and calculate their corresponding mortality risk and length of stay. DESIGN: Retrospective cohort study. SETTING: Seven intensive care units at a large, academic, tertiary medical center. PATIENTS: Adult patients without evidence of end-stage renal disease with more than two creatinine measurements and at least a 6-hr urine output recording who were admitted to the intensive care unit between 2001 and 2007. INTERVENTIONS: Medical records of all the patients were reviewed. Demographic information, laboratory results, charted data, discharge diagnoses, physiological data, and patient outcomes were extracted from the Multiparameter Intelligent Monitoring in Intensive Care II database using a SQL query. MEASUREMENTS AND MAIN RESULTS: From 19,677 adult patient records, 14,524 patients met the inclusion criteria. Fifty-seven percent developed acute kidney injury during their intensive care unit stay. Inhospital mortality rates were: 13.9%, 16.4%, 33.8% for acute kidney injury 1, 2, and 3, respectively, compared with only 6.2% in patients without acute kidney injury (p < .0001). After adjusting for multiple covariates, acute kidney injury was associated with increased hospital mortality (odds ratio 1.4 and 1.3 for acute kidney injury 1 and acute kidney injury 2 and 2.5 for acute kidney injury 3; p < .0001). Using multivariate logistic regression, we found that in patients who developed acute kidney injury, urine output alone was a better mortality predictor than creatinine alone or the combination of both. CONCLUSIONS: More than 50% of our critically ill patients developed some stage of acute kidney injury resulting in a stagewise increased mortality risk. However, the mortality risk associated with acute kidney injury stages 1 and 2 does not differ significantly. In light of these findings, re-evaluation of the Acute Kidney Injury Network staging criteria should be considered.